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1.
Online Journal of Rural Research & Policy ; 17(2):1-20, 2022.
Article in English | CAB Abstracts | ID: covidwho-2024871

ABSTRACT

The COVID-19 pandemic has generated social and economic disruptions, resulting in cascading e ects on the health and well- being of global citizens. However, little research has focused on how COVID-19 has a ected rural regions, despite rurality being a critical factor for understanding community impact and response to the pandemic. The purpose of this phenomenological study was to explore the experiences of rural Nebraskan parents with young children during the COVID-19 pandemic and school shutdown, and the strategies they used to support their families during that time. We conducted individual and group interviews with 22 white, non-Hispanic mothers living in rural towns, villages, and farms in the Great Plains region of the United States. Thematic analysis was used to generate the following themes related to pandemic challenges: Impacts on Children's Education and Development, Impact on Parent's Work, and Social-Emotional Impacts. Additionally, we generated themes related to the ways that rural parents responded to those challenges: Successful Parenting Strategies, Children's Strategies, Using Community Provided Resources, Finding Unexpected Bene ts, and Hope. This study is meaningful because it documented the impact of the COVID-19 pandemic and school shutdown on rural families with young children, and their responses to pandemic-related stressors. Our ndings provide further insights into families' experiences of how COVID-19 a ected their lives. Limitations and future directions are also discussed.

2.
Drug Topics ; 165(4):6-8, 2021.
Article in English | Scopus | ID: covidwho-2010891
3.
Therapeutic Advances in Drug Safety ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2009328

ABSTRACT

Pharmacovigilance (PV) came suddenly into the spotlight when several new vaccines, developed as a response to the COVID-19 pandemic, received emergency authorisation and were rolled out on a large scale in late 2020. The vaccines underwent stringent clinical trials and evaluation from regulatory authorities, but with the use of novel technology and an anticipated rapid and vast deployment of the vaccines, the importance of a well-functioning international post marketing safety surveillance system was stressed. International PV stakeholders were faced with several challenges due to the extent of the global vaccination campaign. The unprecedented volume of reports of suspected adverse events following immunization has led to the development and use of new tools. Furthermore, the collaboration between various PV stakeholders was encouraged and strengthened. PV rose to the challenges posed by the currently ongoing global COVID-19 vaccination campaign and successful adaptations were made in a short period of time. However, the pandemic has not ended yet, the vaccination campaign is far from being completed, and further challenges are anticipated. Advances made during the pandemic will be important to strengthen PV in future and ensure to advance medicines’ safety together. Plain Language Summary: Global safety monitoring of the COVID-19 vaccines: challenges, preparations, and outlooks Pharmacovigilance (PV) is the umbrella term for all sciences and activities relating to the detection, assessment, understanding, and prevention of adverse effects relating to medicines or vaccines. PV came into the spotlight when several new vaccines were authorised and rolled out as a response to the COVID-19 pandemic. The anticipated extent of the global vaccine rollout stressed the importance of a well-functioning safety surveillance system and international collaborations between patients, health care workers, vaccine producers, regulatory authorities, and PV centres. The identification and communication of potential safety concerns showed that adaptations to PV processes made in a short period of time as well as international collaborations were successful. However, it is important to learn from experiences made so far and to make sure the positive advances are maintained in the future to advance medicines’ safety together.

4.
Journal of Obstetrics and Gynaecology Canada ; 44(5):607-608, 2022.
Article in English | EMBASE | ID: covidwho-2004257

ABSTRACT

Objectives: Evaluate peripartum outcomes following COVID-19 vaccination during pregnancy. Methods: Ontario population-based retrospective cohort between December 14, 2020 and September 30, 2021 using linkage of provincial birth registry and COVID-19 immunization databases. Poisson regression was used to generate risk ratios (RR) and 95% confidence intervals (CI), adjusted for temporal, socio-demographic, and clinical factors using propensity scores. Obstetric (postpartum hemorrhage, chorioamnionitis, cesarean birth) and newborn (NICU admission and 5-minute Apgar<7) outcomes were compared for those who received ≥1 dose of COVID-19 vaccine during pregnancy with 2 unexposed groups—Group 1: individuals vaccinated postpartum, Group 2: never vaccinated. Results: Among 97 590 individuals, 22 660 (23%) received ≥1 dose of vaccine during pregnancy (64% received dose 1 in 3rd trimester). Compared with those vaccinated postpartum, we found no increased risks of postpartum hemorrhage (aRR 0.91, 95% CI 0.82–1.02);chorioamnionitis (aRR 0.92, 95% CI 0.70–1.21);or cesarean (aRR 0.92, 95% CI 0.89–0.95) following COVID-19 vaccination, nor any increased risk of NICU admission or 5-minute Apgar <7. All findings were similar when compared with individuals who did not receive COVID-19 vaccination at any point. We did not observe any difference according to vaccine product, number of doses received during pregnancy, or trimester of dose 1. Conclusions: As of late 2021, there is limited evidence from comparative studies in large populations on outcomes following COVID-19 vaccination during pregnancy. Our study of births up to September 30, 2021 did not identify any increased adverse peripartum outcomes associated with later pregnancy COVID-19 vaccination. Once more individuals vaccinated earlier in pregnancy deliver, we will report on other important obstetric and perinatal outcomes. Keywords: COVID-19 vaccine;pregnancy;epidemiology

5.
Studies in Global Social History ; 45:385-389, 2022.
Article in English | Scopus | ID: covidwho-1962535
6.
2022 Joint Rail Conference, JRC 2022 ; 2022.
Article in English | Scopus | ID: covidwho-1962037

ABSTRACT

The Railway industry is facing a productivity issue as is often publicised with regular delays in rolling stock projects [1]. Plus, there is a growing need for innovation in remote services and management that have become the new normal during the COVID-19 pandemic. It drives a need for better Systems Engineering (SE) methods which include increased automation and dependence between systems and system performance, increasing number of disparate specialist engineering teams. [2] The aim of this paper is to develop an adaptable model which expresses the operational behavior of a train system in different railway environments, this model will be quickly and accurately configured to a specific environment to define the needs for a specific passenger service mission. Preventing late changes (cost and time-saving) by generating the right system requirements at the very early design phase through agile Model-Based Systems Engineering (MBSE) approach is the key benefit. Another goal includes increased productivity by minimizing unnecessary manual transcription of concepts when coordinating the work of large teams. This Generic* functional model of a Rolling Stock system can be configured to define specific products for an operator or Original Equipment Manufacturer (OEM). Copyright © 2022 by ASME

7.
European Stroke Journal ; 7(1 SUPPL):452, 2022.
Article in English | EMBASE | ID: covidwho-1928127

ABSTRACT

Background and aims: To observe how the Covid-19 pandemic affected trends in referrals to our tertiary hyperacute stroke unit (HASU). Methods: Referrals from emergency departments in hospitals within our sector were made electronically using the online 'Refer-A-Patient' system. We reviewed 150 referrals made post-Covid, from 16th March 2020 (when Covid restrictions were first introduced in the UK) until June 2020. These were compared with 150 referrals made pre-Covid, between March and June in 2019. Results: The patients in the pre-Covid referral cohort were significantly older on average than the post-Covid referral cohort (p=0.0476);there were more referrals under the age of 50, and fewer over the age of 80, post-Covid. We accepted significantly fewer patients for transfer post-Covid compared with pre-Covid (21% vs. 43% respectively, p=0.0001). The percentage of cases with a confirmed stroke diagnosis post-transfer was marginally higher post-Covid than pre-Covid (69% vs. 59% respectively, p=0.2443). Importantly, of the patients not accepted for transfer post-Covid, none had a subsequent stroke diagnosis. Conclusions: The Covid-19 pandemic seems to have led to a more selective approach in accepting referrals for transfer. This in turn appears to have reduced our stroke mimic rate. This poses an argument that there are benefits in being more selective. Video triage is an emerging tool, which can be used in emergency departments to aid the accuracy of selection for transfer and warrants further evaluation.

8.
Journal of Paediatrics and Child Health ; 58(SUPPL 2):97-98, 2022.
Article in English | EMBASE | ID: covidwho-1916250

ABSTRACT

Background: COVID-19 trials took <1 year to identify therapies reducing death in >30,000 patients but the Australian Placental Transfusion Study took >12 years to show that delaying cord clamping reduced death or major disability (cerebral palsy, severe visual loss, deafness, or cognitive delay) in 1,531 preterm infants. What can this teach us? Further, as composite outcomes of death or major disability can be inconclusive if each is unequally affected (as in the NeOProM Collaboration1) 2 important aims are (i) global co-operation (https://www.alphacollaboration.com/) to identify core Participant-Intervention-Comparator-Outcome questions for trials assessing mortality, a key outcome, and (ii) to answer those questions in much larger, faster trials. Such trials will also yield much more precise estimates of disability in survivors than was previously typical - a major benefit. Method: To inform these aims we compared enrolment in 2 COVID-19 trials and in 10 trials by IMPACT collaborators with samples >1,500 in high- or low-or-middle-income countries (HIC/LMIC). Results: The COVID-19 trials took 3-9 months, enrolling 13 - 219 per-site-per-year. Perinatal trials took 16-86 months, enrolling 5 - 1,700 per site per year. Trials in pregnant women or LMIC (n = 53,092) enrolled 5 times more than trials in newborns or restricted to HIC (n = 9,014). (Table) Conclusions: Greater international collaboration could resolve questions of shared relevance and priority more rapidly. Megatrials addressing mortality may benefit from highly streamlined processes for enrolment and minimal data collection, e.g., RECOVERY's one-page outcome form.

9.
Topics in Antiviral Medicine ; 30(1 SUPPL):94, 2022.
Article in English | EMBASE | ID: covidwho-1880132

ABSTRACT

Background: It is imperative to investigate novel, broadly conserved coronavirus immunogens as new SARS-CoV-2 variants of concern are continually emerging. The goal of this study was to generate a broadly protective long-term vaccine candidate against potential new variants of SARS-CoV-2 and novel, outbreak coronaviruses. The vaccine immunogen spanned portions of the highly conserved RNA replication machinery (nsp12 and nsp13) (CoV.Con). The vaccine was packaged into a rhesus adenoviral vector (RhAd52.CoV.Con) with the goal of generating robust long-lived CD8+ T-cell responses. Methods: The CoV.Con immunogen was generated by aligning coronavirus sequences to determine the most conserved region. ACE2 carrier and BALB/c mice were immunized intramuscularly with 109 RhAd52.CoV.Con and boosted four weeks later. Splenocytes were harvested four weeks after boost. Cellular immunity was determined through ELIspot and intracellular cytokine stain (ICS). BALB/c mice were primed and boosted with RhAd52.CoV.Con. Four weeks post boost mice were challenged intranasally with mouse adapted SARS-CoV-2. Protection was measured by weight loss and plaque assay. Results: Four weeks post RhAd52.CoV.Con boost immunization, ACE2 carrier and BALB/c mice developed cellular immunity as shown by ELIspot (Fig 1a) and ICS. ACE2 carrier mice cellular immunity showed bias toward nsp12 while BALB/c mice showed nsp13 preference. BALB/c mice were primed and boosted with RhAd52.CoV.Con. Four weeks after boost mice were challenged with mouse adapted SARS-CoV-2. RhAd52.CoV.Con was compared against and combined with a suboptimal dose of RhAd52.S.pp at 4 and 8 weeks post injection. Protection against weight loss (Fig 1b) and viral load (Fig 1c) was minimal although increased RhAd52.S.pp protection was observed from 4 to 8 weeks post immunization. Increased RhAd52.S.pp protection corresponded to increased spike antibody binding and neutralizing titers. Conclusion: Our work investigates a highly conserved coronavirus immunogen, CoV.Con, demonstrating immunogenicity in two mouse strains. While RhAd52. CoV.Con protection in the mouse model was minimal it demonstrates a schema for generating coronavirus immunogens that can protect against multiple different viruses. This work takes the first steps towards generating a long-lived broadly protective T-cell coronavirus vaccine.

10.
Journal of Oncology Pharmacy Practice ; 28(2 SUPPL):29-30, 2022.
Article in English | EMBASE | ID: covidwho-1868952

ABSTRACT

Background: Patient satisfaction with non-medical prescriber (NMP) clinics at the Churchill Cancer Centre (Oxford University Hospitals NHS Foundation Trust) has been reported previously.1 Patient consultations, (face to face or telephone) by prescribing pharmacists in uro-oncology clinics (mostly prostate cancer) have increased significantly and the scope of the role is expanding from cycle 2+clinical reviews to treatment initiation, consent and cycle 1 prescribing. Objectives • To quantify the increase in patient numbers seen or telephoned in prescribing pharmacist clinics, both as whole numbers and as a proportion of the Uro-oncology service (medical oncology). • To identify how the role of the prescribing pharmacist role is expanding to patient care at earlier stages in the treatment pathway. Method: Contribution to the uro-oncology service has been measured using the following parameters (see Table 1). • Number of patient consultations in prescribing pharmacist clinics over the past 12 months, using data from the Trust's Electronic Prescribing and Medicines Administration system. • Proportion of these patient contacts as a percentage of the overall uro-oncology service. • And compared to prior year. Results: In the 12 months to June 2021:- • Uro-oncology prescribing pharmacists have seen or telephoned 61% more patients than the previous 12 months. • 78% of the 889 patient contacts were telemedicine consultations, compared to 20% in the prior 12 months. This is due to the covid pandemic. • The contribution of prescribing pharmacist consultations to the overall uro-oncology service has increased by 7%. Discussion: At the Churchill Cancer Centre two prescribing pharmacists see or telephone an average of 21-24 patients per week. Current scope of the prescribing pharmacist role comprises clinical review of metastatic prostate cancer patients being treated with: luteinizing hormone-releasing hormone (LHRH) agonists, with or without bicalutamide, enzalutamide, abiraterone, docetaxel, cabazitaxel. Clinical consultations typically include: assessment of treatment efficacy and tolerability, prescribing continued treatment, or referral to Consultant, addition of bicalutamide (PSA relapse) or stopping bicalutamide (for PSA withdrawal response), ordering CT or MRI scan if appropriate, managing symptoms e.g. medroxyprogesterone / cyproterone for hot flushes, requesting GP to initiate bone protection (bisphosphonate). The expanding scope of the role includes: liaison with MDT / Consultant for diagnosis and treatment, consenting patient for treatment, cycle 1 prescribing, oral education session prior to starting treatment (patient counselling including safety netting, clinical checks, drug interactions, drug supply). Adherence to treatment pathway (e.g. enzalutamide) to ensure correct blood tests ordered and timing of next clinic review. Conclusion: Prescribing pharmacist clinics enable follow up and treatment of large numbers of uro-oncology patients. The covid pandemic has driven trends for oral systemic anticancer treatment (e.g. enzalutamide) and telemedicine consultations. Expanding the role of the prescribing pharmacist to treatment initiation, patient consent, and cycle 1 prescribing can improve the efficiency of the clinical service and bring opportunities for enhanced skills and development.

11.
Oncology Nursing Forum ; 49(2):E46-E47, 2022.
Article in English | Web of Science | ID: covidwho-1849322
12.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335180

ABSTRACT

Background Antibodies are crucial for vaccine-mediated protection against many pathogens. Modifications to vaccine delivery that increase antibody magnitude, longevity, and/or quality are therefore of great interest for maximising efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6mo) – using AS01 B -adjuvanted RH5.1 malaria antigen – substantially improves serum IgG durability as compared to monthly dosing (0-1-2mo;NCT02927145 ). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing was unclear. Methods Immunokinetics of PfRH5-specific Ig across multiple isotypes were compared between DFx and monthly regimen vaccinees. Peak responses were characterised in-depth with a systems serology platform including biophysical and functional profiling. Computational modelling was used to define the humoral feature set associated with DFx dosing. PfRH5-specific B cells were quantified by flow cytometry and sorted for single cell RNA sequencing (scRNA-seq). Differential gene expression between DFx and monthly dosing regimens was explored with Seurat, DESeq2 and gene set enrichment analysis. Results DFx dosing increases the frequency of circulating PfRH5-specific B cells and longevity of PfRH5-specific IgG1, as well as other isotypes and subclasses. At the peak antibody response, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn-binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. At the same time point, scRNA-seq of PfRH5-specific B cells revealed enriched plasma cell and Ig / protein export signals in the monthly dosing group as compared to DFx vaccinees. Conclusions DFx dosing of the RH5.1/AS01 B vaccine had a profound impact on the humoral response. Our data suggest plausible mechanisms relating to improved FcRn-binding (known to improve Ig longevity) and a potential shift from short-lived to long-lived plasma cells. Recent reports of the positive impact of delayed boosting on SARS-CoV-2 vaccine immunogenicity highlight the broad relevance of these data.

13.
Journal of the Australasian Tax Teachers Association ; 15:142-164, 2020.
Article in English | Scopus | ID: covidwho-1777172

ABSTRACT

Equity crowdfunding facilitates companies’ access to capital, particularly for start-ups. In New Zealand, light-handed regulation and a syndication model have contributed to the growth of equity crowdfunding. This article analyses the effects of income tax legislation on crowdfunding in New Zealand and considers how — and whether — amendments to income tax legislation could further promote this form of private investment. This paper argues that dissonance exists between financial markets policy on crowdfunding and tax policy on research and development. In the context of dire predictions for Covid-19-related job losses, the potential for crowdfunding to promote start-ups, and to create jobs, deserves tax policymakers’ attention. © 2020, Australasian Tax Teachers' Association. All rights reserved.

14.
McCrone, J. T.; Hill, V.; Bajaj, S.; Pena, R. E.; Lambert, B. C.; Inward, R.; Bhatt, S.; Volz, E.; Ruis, C.; Dellicour, S.; Baele, G.; Zarebski, A. E.; Sadilek, A.; Wu, N.; Schneider, A.; Ji, X.; Raghwani, J.; Jackson, B.; Colquhoun, R.; O'Toole, Á, Peacock, T. P.; Twohig, K.; Thelwall, S.; Dabrera, G.; Myers, R.; Faria, N. R.; Huber, C.; Bogoch, I. I.; Khan, K.; du Plessis, L.; Barrett, J. C.; Aanensen, D. M.; Barclay, W. S.; Chand, M.; Connor, T.; Loman, N. J.; Suchard, M. A.; Pybus, O. G.; Rambaut, A.; Kraemer, M. U. G.; Robson, S. C.; Connor, T. R.; Loman, N. J.; Golubchik, T.; Martinez Nunez, R. T.; Bonsall, D.; Rambaut, A.; Snell, L. B.; Livett, R.; Ludden, C.; Corden, S.; Nastouli, E.; Nebbia, G.; Johnston, I.; Lythgoe, K.; Estee Torok, M.; Goodfellow, I. G.; Prieto, J. A.; Saeed, K.; Jackson, D. K.; Houlihan, C.; Frampton, D.; Hamilton, W. L.; Witney, A. A.; Bucca, G.; Pope, C. F.; Moore, C.; Thomson, E. C.; Harrison, E. M.; Smith, C. P.; Rogan, F.; Beckwith, S. M.; Murray, A.; Singleton, D.; Eastick, K.; Sheridan, L. A.; Randell, P.; Jackson, L. M.; Ariani, C. V.; Gonçalves, S.; Fairley, D. J.; Loose, M. W.; Watkins, J.; Moses, S.; Nicholls, S.; Bull, M.; Amato, R.; Smith, D. L.; Aanensen, D. M.; Barrett, J. C.; Aggarwal, D.; Shepherd, J. G.; Curran, M. D.; Parmar, S.; Parker, M. D.; Williams, C.; Glaysher, S.; Underwood, A. P.; Bashton, M.; Pacchiarini, N.; Loveson, K. F.; Byott, M.; Carabelli, A. M.; Templeton, K. E.; de Silva, T. I.; Wang, D.; Langford, C. F.; Sillitoe, J.; Gunson, R. N.; Cottrell, S.; O'Grady, J.; Kwiatkowski, D.; Lillie, P. J.; Cortes, N.; Moore, N.; Thomas, C.; Burns, P. J.; Mahungu, T. W.; Liggett, S.; Beckett, A. H.; Holden, M. T. G.; Levett, L. J.; Osman, H.; Hassan-Ibrahim, M. O.; Simpson, D. A.; Chand, M.; Gupta, R. K.; Darby, A. C.; Paterson, S.; Pybus, O. G.; Volz, E. M.; de Angelis, D.; Robertson, D. L.; Page, A. J.; Martincorena, I.; Aigrain, L.; Bassett, A. R.; Wong, N.; Taha, Y.; Erkiert, M. J.; Spencer Chapman, M. H.; Dewar, R.; McHugh, M. P.; Mookerjee, S.; Aplin, S.; Harvey, M.; Sass, T.; Umpleby, H.; Wheeler, H.; McKenna, J. P.; Warne, B.; Taylor, J. F.; Chaudhry, Y.; Izuagbe, R.; Jahun, A. S.; Young, G. R.; McMurray, C.; McCann, C. M.; Nelson, A.; Elliott, S.; Lowe, H.; Price, A.; Crown, M. R.; Rey, S.; Roy, S.; Temperton, B.; Shaaban, S.; Hesketh, A. R.; Laing, K. G.; Monahan, I. M.; Heaney, J.; Pelosi, E.; Silviera, S.; Wilson-Davies, E.; Fryer, H.; Adams, H.; du Plessis, L.; Johnson, R.; Harvey, W. T.; Hughes, J.; Orton, R. J.; Spurgin, L. G.; Bourgeois, Y.; Ruis, C.; O'Toole, Á, Gourtovaia, M.; Sanderson, T.; Fraser, C.; Edgeworth, J.; Breuer, J.; Michell, S. L.; Todd, J. A.; John, M.; Buck, D.; Gajee, K.; Kay, G. L.; Peacock, S. J.; Heyburn, D.; Kitchman, K.; McNally, A.; Pritchard, D. T.; Dervisevic, S.; Muir, P.; Robinson, E.; Vipond, B. B.; Ramadan, N. A.; Jeanes, C.; Weldon, D.; Catalan, J.; Jones, N.; da Silva Filipe, A.; Williams, C.; Fuchs, M.; Miskelly, J.; Jeffries, A. R.; Oliver, K.; Park, N. R.; Ash, A.; Koshy, C.; Barrow, M.; Buchan, S. L.; Mantzouratou, A.; Clark, G.; Holmes, C. W.; Campbell, S.; Davis, T.; Tan, N. K.; Brown, J. R.; Harris, K. A.; Kidd, S. P.; Grant, P. R.; Xu-McCrae, L.; Cox, A.; Madona, P.; Pond, M.; Randell, P. A.; Withell, K. T.; Williams, C.; Graham, C.; Denton-Smith, R.; Swindells, E.; Turnbull, R.; Sloan, T. J.; Bosworth, A.; Hutchings, S.; Pymont, H. M.; Casey, A.; Ratcliffe, L.; Jones, C. R.; Knight, B. A.; Haque, T.; Hart, J.; Irish-Tavares, D.; Witele, E.; Mower, C.; Watson, L. K.; Collins, J.; Eltringham, G.; Crudgington, D.; Macklin, B.; Iturriza-Gomara, M.; Lucaci, A. O.; McClure, P. C.; Carlile, M.; Holmes, N.; Moore, C.; Storey, N.; Rooke, S.; Yebra, G.; Craine, N.; Perry, M.; Alikhan, N. F.; Bridgett, S.; Cook, K. F.; Fearn, C.; Goudarzi, S.; Lyons, R. A.; Williams, T.; Haldenby, S. T.; Durham, J.; Leonard, S.; Davies, R. M.; Batra, R.; Blane, B.; Spyer, M. J.; Smith, P.; Yavus, M.; Williams, R. J.; Mahanama, A. I. K.; Samaraweera, B.; Girgis, S. T.; Hansford, S. E.; Green, A.; Beaver, C.; Bellis, K. L.; Dorman, M. J.; Kay, S.; Prestwood, L.; Rajatileka, S.; Quick, J.; Poplawski, R.; Reynolds, N.; Mack, A.; Morriss, A.; Whalley, T.; Patel, B.; Georgana, I.; Hosmillo, M.; Pinckert, M. L.; Stockton, J.; Henderson, J. H.; Hollis, A.; Stanley, W.; Yew, W. C.; Myers, R.; Thornton, A.; Adams, A.; Annett, T.; Asad, H.; Birchley, A.; Coombes, J.; Evans, J. M.; Fina, L.; Gatica-Wilcox, B.; Gilbert, L.; Graham, L.; Hey, J.; Hilvers, E.; Jones, S.; Jones, H.; Kumziene-Summerhayes, S.; McKerr, C.; Powell, J.; Pugh, G.; Taylor, S.; Trotter, A. J.; Williams, C. A.; Kermack, L. M.; Foulkes, B. H.; Gallis, M.; Hornsby, H. R.; Louka, S. F.; Pohare, M.; Wolverson, P.; Zhang, P.; MacIntyre-Cockett, G.; Trebes, A.; Moll, R. J.; Ferguson, L.; Goldstein, E. J.; Maclean, A.; Tomb, R.; Starinskij, I.; Thomson, L.; Southgate, J.; Kraemer, M. U. G.; Raghwani, J.; Zarebski, A. E.; Boyd, O.; Geidelberg, L.; Illingworth, C. J.; Jackson, C.; Pascall, D.; Vattipally, S.; Freeman, T. M.; Hsu, S. N.; Lindsey, B. B.; James, K.; Lewis, K.; Tonkin-Hill, G.; Tovar-Corona, J. M.; Cox, M.; Abudahab, K.; Menegazzo, M.; Taylor, B. E. W.; Yeats, C. A.; Mukaddas, A.; Wright, D. W.; de Oliveira Martins, L.; Colquhoun, R.; Hill, V.; Jackson, B.; McCrone, J. T.; Medd, N.; Scher, E.; Keatley, J. P.; Curran, T.; Morgan, S.; Maxwell, P.; Smith, K.; Eldirdiri, S.; Kenyon, A.; Holmes, A. H.; Price, J. R.; Wyatt, T.; Mather, A. E.; Skvortsov, T.; Hartley, J. A.; Guest, M.; Kitchen, C.; Merrick, I.; Munn, R.; Bertolusso, B.; Lynch, J.; Vernet, G.; Kirk, S.; Wastnedge, E.; Stanley, R.; Idle, G.; Bradley, D. T.; Poyner, J.; Mori, M.; Jones, O.; Wright, V.; Brooks, E.; Churcher, C. M.; Fragakis, M.; Galai, K.; Jermy, A.; Judges, S.; McManus, G. M.; Smith, K. S.; Westwick, E.; Attwood, S. W.; Bolt, F.; Davies, A.; De Lacy, E.; Downing, F.; Edwards, S.; Meadows, L.; Jeremiah, S.; Smith, N.; Foulser, L.; Charalampous, T.; Patel, A.; Berry, L.; Boswell, T.; Fleming, V. M.; Howson-Wells, H. C.; Joseph, A.; Khakh, M.; Lister, M. M.; Bird, P. W.; Fallon, K.; Helmer, T.; McMurray, C. L.; Odedra, M.; Shaw, J.; Tang, J. W.; Willford, N. J.; Blakey, V.; Raviprakash, V.; Sheriff, N.; Williams, L. A.; Feltwell, T.; Bedford, L.; Cargill, J. S.; Hughes, W.; Moore, J.; Stonehouse, S.; Atkinson, L.; Lee, J. C. D.; Shah, D.; Alcolea-Medina, A.; Ohemeng-Kumi, N.; Ramble, J.; Sehmi, J.; Williams, R.; Chatterton, W.; Pusok, M.; Everson, W.; Castigador, A.; Macnaughton, E.; El Bouzidi, K.; Lampejo, T.; Sudhanva, M.; Breen, C.; Sluga, G.; Ahmad, S. S. Y.; George, R. P.; Machin, N. W.; Binns, D.; James, V.; Blacow, R.; Coupland, L.; Smith, L.; Barton, E.; Padgett, D.; Scott, G.; Cross, A.; Mirfenderesky, M.; Greenaway, J.; Cole, K.; Clarke, P.; Duckworth, N.; Walsh, S.; Bicknell, K.; Impey, R.; Wyllie, S.; Hopes, R.; Bishop, C.; Chalker, V.; et al..
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326827

ABSTRACT

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases1-3. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions4,5. Here we analyse 52,992 Delta genomes from England in combination with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction to and regional dissemination across England, in the context of changing travel and social restrictions. Through analysis of human movement, contact tracing, and virus genomic data, we find that the focus of geographic expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced >1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers from India reduced onward transmission from importations;however the transmission chains that later dominated the Delta wave in England had been already seeded before restrictions were introduced. In England, increasing inter-regional travel drove Delta's nationwide dissemination, with some cities receiving >2,000 observable lineage introductions from other regions. Subsequently, increased levels of local population mixing, not the number of importations, was associated with faster relative growth of Delta. Among US states, we find that regions that previously experienced large waves also had faster Delta growth rates, and a model including interactions between immunity and human behaviour could accurately predict the rise of Delta there. Delta's invasion dynamics depended on fine scale spatial heterogeneity in immunity and contact patterns and our findings will inform optimal spatial interventions to reduce transmission of current and future VOCs such as Omicron.

15.
Robson, S. C.; Connor, T. R.; Loman, N. J.; Golubchik, T.; Nunez, R. T. M.; Bonsall, D.; Rambaut, A.; Snell, L. B.; Livett, R.; Ludden, C.; Corden, S.; Nastouli, E.; Nebbia, G.; Johnston, I.; Lythgoe, K.; Torok, M. E.; Goodfellow, I. G.; Prieto, J. A.; Saeed, K.; Jackson, D. K.; Houlihan, C.; Frampton, D.; Hamilton, W. L.; Witney, A. A.; Bucca, G.; Pope, C. F.; Moore, C.; Thomson, E. C.; Harrison, E. M.; Smith, C. P.; Rogan, F.; Beckwith, S. M.; Murray, A.; Singleton, D.; Eastick, K.; Sheridan, L. A.; Randell, P.; Jackson, L. M.; Ariani, C. V.; Gonçalves, S.; Fairley, D. J.; Loose, M. W.; Watkins, J.; Moses, S.; Nicholls, S.; Bull, M.; Amato, R.; Smith, D. L.; Aanensen, D. M.; Barrett, J. C.; Aggarwal, D.; Shepherd, J. G.; Curran, M. D.; Parmar, S.; Parker, M. D.; Williams, C.; Glaysher, S.; Underwood, A. P.; Bashton, M.; Loveson, K. F.; Byott, M.; Pacchiarini, N.; Carabelli, A. M.; Templeton, K. E.; de Silva, T. I.; Wang, D.; Langford, C. F.; Sillitoe, J.; Gunson, R. N.; Cottrell, S.; O'Grady, J.; Kwiatkowski, D.; Lillie, P. J.; Cortes, N.; Moore, N.; Thomas, C.; Burns, P. J.; Mahungu, T. W.; Liggett, S.; Beckett, A. H.; Holden, M. T. G.; Levett, L. J.; Osman, H.; Hassan-Ibrahim, M. O.; Simpson, D. A.; Chand, M.; Gupta, R. K.; Darby, A. C.; Paterson, S.; Pybus, O. G.; Volz, E. M.; de Angelis, D.; Robertson, D. L.; Page, A. J.; Martincorena, I.; Aigrain, L.; Bassett, A. R.; Wong, N.; Taha, Y.; Erkiert, M. J.; Chapman, M. H. S.; Dewar, R.; McHugh, M. P.; Mookerjee, S.; Aplin, S.; Harvey, M.; Sass, T.; Umpleby, H.; Wheeler, H.; McKenna, J. P.; Warne, B.; Taylor, J. F.; Chaudhry, Y.; Izuagbe, R.; Jahun, A. S.; Young, G. R.; McMurray, C.; McCann, C. M.; Nelson, A.; Elliott, S.; Lowe, H.; Price, A.; Crown, M. R.; Rey, S.; Roy, S.; Temperton, B.; Shaaban, S.; Hesketh, A. R.; Laing, K. G.; Monahan, I. M.; Heaney, J.; Pelosi, E.; Silviera, S.; Wilson-Davies, E.; Adams, H.; du Plessis, L.; Johnson, R.; Harvey, W. T.; Hughes, J.; Orton, R. J.; Spurgin, L. G.; Bourgeois, Y.; Ruis, C.; O'Toole, Á, Gourtovaia, M.; Sanderson, T.; Fraser, C.; Edgeworth, J.; Breuer, J.; Michell, S. L.; Todd, J. A.; John, M.; Buck, D.; Gajee, K.; Kay, G. L.; Peacock, S. J.; Heyburn, D.; Kitchman, K.; McNally, A.; Pritchard, D. T.; Dervisevic, S.; Muir, P.; Robinson, E.; Vipond, B. B.; Ramadan, N. A.; Jeanes, C.; Weldon, D.; Catalan, J.; Jones, N.; da Silva Filipe, A.; Williams, C.; Fuchs, M.; Miskelly, J.; Jeffries, A. R.; Oliver, K.; Park, N. R.; Ash, A.; Koshy, C.; Barrow, M.; Buchan, S. L.; Mantzouratou, A.; Clark, G.; Holmes, C. W.; Campbell, S.; Davis, T.; Tan, N. K.; Brown, J. R.; Harris, K. A.; Kidd, S. P.; Grant, P. R.; Xu-McCrae, L.; Cox, A.; Madona, P.; Pond, M.; Randell, P. A.; Withell, K. T.; Williams, C.; Graham, C.; Denton-Smith, R.; Swindells, E.; Turnbull, R.; Sloan, T. J.; Bosworth, A.; Hutchings, S.; Pymont, H. M.; Casey, A.; Ratcliffe, L.; Jones, C. R.; Knight, B. A.; Haque, T.; Hart, J.; Irish-Tavares, D.; Witele, E.; Mower, C.; Watson, L. K.; Collins, J.; Eltringham, G.; Crudgington, D.; Macklin, B.; Iturriza-Gomara, M.; Lucaci, A. O.; McClure, P. C.; Carlile, M.; Holmes, N.; Moore, C.; Storey, N.; Rooke, S.; Yebra, G.; Craine, N.; Perry, M.; Fearn, N. C.; Goudarzi, S.; Lyons, R. A.; Williams, T.; Haldenby, S. T.; Durham, J.; Leonard, S.; Davies, R. M.; Batra, R.; Blane, B.; Spyer, M. J.; Smith, P.; Yavus, M.; Williams, R. J.; Mahanama, A. I. K.; Samaraweera, B.; Girgis, S. T.; Hansford, S. E.; Green, A.; Beaver, C.; Bellis, K. L.; Dorman, M. J.; Kay, S.; Prestwood, L.; Rajatileka, S.; Quick, J.; Poplawski, R.; Reynolds, N.; Mack, A.; Morriss, A.; Whalley, T.; Patel, B.; Georgana, I.; Hosmillo, M.; Pinckert, M. L.; Stockton, J.; Henderson, J. H.; Hollis, A.; Stanley, W.; Yew, W. C.; Myers, R.; Thornton, A.; Adams, A.; Annett, T.; Asad, H.; Birchley, A.; Coombes, J.; Evans, J. M.; Fina, L.; Gatica-Wilcox, B.; Gilbert, L.; Graham, L.; Hey, J.; Hilvers, E.; Jones, S.; Jones, H.; Kumziene-Summerhayes, S.; McKerr, C.; Powell, J.; Pugh, G.; Taylor, S.; Trotter, A. J.; Williams, C. A.; Kermack, L. M.; Foulkes, B. H.; Gallis, M.; Hornsby, H. R.; Louka, S. F.; Pohare, M.; Wolverson, P.; Zhang, P.; MacIntyre-Cockett, G.; Trebes, A.; Moll, R. J.; Ferguson, L.; Goldstein, E. J.; Maclean, A.; Tomb, R.; Starinskij, I.; Thomson, L.; Southgate, J.; Kraemer, M. U. G.; Raghwani, J.; Zarebski, A. E.; Boyd, O.; Geidelberg, L.; Illingworth, C. J.; Jackson, C.; Pascall, D.; Vattipally, S.; Freeman, T. M.; Hsu, S. N.; Lindsey, B. B.; James, K.; Lewis, K.; Tonkin-Hill, G.; Tovar-Corona, J. M.; Cox, M.; Abudahab, K.; Menegazzo, M.; Taylor, B. E. W.; Yeats, C. A.; Mukaddas, A.; Wright, D. W.; de Oliveira Martins, L.; Colquhoun, R.; Hill, V.; Jackson, B.; McCrone, J. T.; Medd, N.; Scher, E.; Keatley, J. P.; Curran, T.; Morgan, S.; Maxwell, P.; Smith, K.; Eldirdiri, S.; Kenyon, A.; Holmes, A. H.; Price, J. R.; Wyatt, T.; Mather, A. E.; Skvortsov, T.; Hartley, J. A.; Guest, M.; Kitchen, C.; Merrick, I.; Munn, R.; Bertolusso, B.; Lynch, J.; Vernet, G.; Kirk, S.; Wastnedge, E.; Stanley, R.; Idle, G.; Bradley, D. T.; Poyner, J.; Mori, M.; Jones, O.; Wright, V.; Brooks, E.; Churcher, C. M.; Fragakis, M.; Galai, K.; Jermy, A.; Judges, S.; McManus, G. M.; Smith, K. S.; Westwick, E.; Attwood, S. W.; Bolt, F.; Davies, A.; De Lacy, E.; Downing, F.; Edwards, S.; Meadows, L.; Jeremiah, S.; Smith, N.; Foulser, L.; Charalampous, T.; Patel, A.; Berry, L.; Boswell, T.; Fleming, V. M.; Howson-Wells, H. C.; Joseph, A.; Khakh, M.; Lister, M. M.; Bird, P. W.; Fallon, K.; Helmer, T.; McMurray, C. L.; Odedra, M.; Shaw, J.; Tang, J. W.; Willford, N. J.; Blakey, V.; Raviprakash, V.; Sheriff, N.; Williams, L. A.; Feltwell, T.; Bedford, L.; Cargill, J. S.; Hughes, W.; Moore, J.; Stonehouse, S.; Atkinson, L.; Lee, J. C. D.; Shah, D.; Alcolea-Medina, A.; Ohemeng-Kumi, N.; Ramble, J.; Sehmi, J.; Williams, R.; Chatterton, W.; Pusok, M.; Everson, W.; Castigador, A.; Macnaughton, E.; Bouzidi, K. El, Lampejo, T.; Sudhanva, M.; Breen, C.; Sluga, G.; Ahmad, S. S. Y.; George, R. P.; Machin, N. W.; Binns, D.; James, V.; Blacow, R.; Coupland, L.; Smith, L.; Barton, E.; Padgett, D.; Scott, G.; Cross, A.; Mirfenderesky, M.; Greenaway, J.; Cole, K.; Clarke, P.; Duckworth, N.; Walsh, S.; Bicknell, K.; Impey, R.; Wyllie, S.; Hopes, R.; Bishop, C.; Chalker, V.; Harrison, I.; Gifford, L.; Molnar, Z.; Auckland, C.; Evans, C.; Johnson, K.; Partridge, D. G.; Raza, M.; Baker, P.; Bonner, S.; Essex, S.; Murray, L. J.; Lawton, A. I.; Burton-Fanning, S.; Payne, B. A. I.; Waugh, S.; Gomes, A. N.; Kimuli, M.; Murray, D. R.; Ashfield, P.; Dobie, D.; Ashford, F.; Best, A.; Crawford, L.; Cumley, N.; Mayhew, M.; Megram, O.; Mirza, J.; Moles-Garcia, E.; Percival, B.; Driscoll, M.; Ensell, L.; Lowe, H. L.; Maftei, L.; Mondani, M.; Chaloner, N. J.; Cogger, B. J.; Easton, L. J.; Huckson, H.; Lewis, J.; Lowdon, S.; Malone, C. S.; Munemo, F.; Mutingwende, M.; et al..
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326811

ABSTRACT

The scale of data produced during the SARS-CoV-2 pandemic has been unprecedented, with more than 5 million sequences shared publicly at the time of writing. This wealth of sequence data provides important context for interpreting local outbreaks. However, placing sequences of interest into national and international context is difficult given the size of the global dataset. Often outbreak investigations and genomic surveillance efforts require running similar analyses again and again on the latest dataset and producing reports. We developed civet (cluster investigation and virus epidemiology tool) to aid these routine analyses and facilitate virus outbreak investigation and surveillance. Civet can place sequences of interest in the local context of background diversity, resolving the query into different 'catchments' and presenting the phylogenetic results alongside metadata in an interactive, distributable report. Civet can be used on a fine scale for clinical outbreak investigation, for local surveillance and cluster discovery, and to routinely summarise the virus diversity circulating on a national level. Civet reports have helped researchers and public health bodies feedback genomic information in the appropriate context within a timeframe that is useful for public health.

16.
Drug Safety ; 44(12):1463, 2021.
Article in English | ProQuest Central | ID: covidwho-1543401

ABSTRACT

Background/Introduction: Disproportionality analysis [1, 2] has been a stalwart of post marketing safety surveillance, however it has some drawbacks. vigiGroup [3, 4] is a novel ICSR clustering method which can complement disproportionality analysis, and we present its first application to prospective monitoring of a drug's safety profile, by incorporating its use into our surveillance activities of the COVID-19 vaccines. Objective/Aim: We aim to explore and develop the utilisation of vigiGroup as a tool for prospective monitoring of COVID-19 vaccine safety reports in VigiBase. Methods: VigiBase receives tens of thousands of adverse event reports per week for all COVID-19 vaccines collectively. Each week, the vigiGroup algorithm has been applied to cluster the accumulated ICSRs of COVID-19 vaccines. The algorithm was applied independently for each vaccine, but also grouping the vaccines by platform. Our multidisciplinary team of pharmacovigilance experts and data scientists have developed powerful data visualisation tools to rapidly explore the evolving safety profile of the vaccines, as well as to strengthen the hypotheses generated with traditional disproportionality analysis. Results: A number of potential safety signals have been identified directly using the tools we have developed in tandem with the vigiGroup clustering algorithm. These include appendicitis and hearing loss/tinnitus for all COVID-19 vaccines and delayed local reactions to the Moderna vaccine, which were identified in a vigiGroup interface with the aid of imbedded data visualisation tools. Several more signals have been strengthened by further incorporating vigiGroup as a complementary tool to traditional disproportionality analysis. We have moreover demonstrated the efficacy of the algorithm and our tools by recovering labelled adverse reactions, such as hypersensitivity and anaphylaxis, and emerging safety signals, e.g. myocarditis, for all of the vaccines. Conclusion: The use of vigiGroup clustering has been explored by pharmacovigilance experts at the Uppsala Monitoring Centre and has been found to be a promising new tool for post-marketing drug safety surveillance. The vigiGroup algorithm and data visualisation tools are being iteratively developed as the prospective monitoring of COVID-19 vaccines continues.

19.
Nephrology Dialysis Transplantation ; 36(SUPPL 1):i245-i246, 2021.
Article in English | EMBASE | ID: covidwho-1402418

ABSTRACT

BACKGROUND AND AIMS: Initial WHO guidance advised cautious fluid administration for patients with COVID-19 due to concern about the development of acute respiratory distress syndrome (ARDS). However, as the pandemic unfolded it became apparent that patients who were admitted to hospital had high rates of AKI and this initiated a change in local clinical guidelines during early April 2020. We aimed to ascertain the impact of judicious intravenous fluid use on mortality, length of hospitalisation and AKI. METHOD: An observational cohort study of 158 adults admitted with confirmed SARS-Cov-2 between 18th March and 9th May 2020 was conducted in a teaching hospital and designated centre for infectious diseases, London, UK. Key clinical and demographic data collected included clinical severity markers on admission, biochemical and haematological parameters as well as radiological findings. Primary outcomes were inpatient mortality, mortality at 6-weeks post discharge, length of hospitalisation and intensive care (ICU) admission. We also measured requirement for kidney replacement therapy (KRT) and AKI recovery rate at discharge. Using tests of difference, we compared key outcomes between patients treated with varying fluid regimens and then identified risk factors for AKI and mortality using multivariate logistic regression with results expressed as odds ratios (OR) with corresponding 95% confidence interval (CI). RESULTS: The median age was 74.4 (IQR 59.90 - 84.35) years, 66% were male, 53% white with hypertension and diabetes being the commonest co-morbidities. The median duration of illness prior to admission was 7 days (IQR 2 - 10) with respiratory symptoms and fever most prevalent. The people who presented with AKI on admission were more likely to receive fluids (34% vs 15%, p=0.02). 118 patients (75%) received fluids within 24-hours of admission with no difference in volume administered after local guidance change (p=0.78). Comparing patients receiving fluids with those who did not, we observed no difference in mortality (p=0.97), duration of hospital stays (p=0.26) or requirement for ICU admission (p=0.70). 18% died as an inpatient, and 52 patients were either admitted with or developed AKI. Of these 52 patients, 43 received fluids and 9 did not with no difference in KRT requirement (p=0.34), mortality (p=0.50) or AKI recovery (p=0.63). Peak AKI stage was greater among participants who received fluids though stage of AKI at presentation was also greater (p=0.04). Mortality rate in patients with an AKI is higher compared to overall inpatient mortality (31% vs 18%). Of the 36 patients with AKI (Figure Presnted) who were discharged home, 25 patients (69.4%) had renal recovery by the time of discharge. Increasing age and clinical severity on admission were associated with higher mortality (see Figure 1). Older age was associated with 34 - 53 times higher risk of death compared with those aged ≥ 65 years (age 76 - 85 years: OR 34.26, 95% CI: 3.94 - 297.48, p=0.001;age > 85 years: OR 53.07, 95% CI: 5.23 - 539.03, p=0.001). Patients with NEWS2 >4 on admission has 5-fold increased risk of death than those with a score ≥4 (OR 5.26, 95% CI: 1.32 - 20.92). Black ethnicity was associated with a 16-fold increased risk of developing AKI (OR 15.86, 95% CI: 1.67 - 150.99). CONCLUSION: To our knowledge, this is the first study to examine the impact of fluid management on inpatient mortality as well as on renal-associated outcomes of COVID-19 admission. Fluid administration regimen did not have an impact on mortality, length of hospitalisation or ICU admission, nor did it affect renal outcomes. Given the high rates of AKI and KRT in COVID-19 disease, early fluid administration is likely to be an important cornerstone of future management. Further adequately powered prospective studies are required to identify whether early fluid administration can reduce renal injury.

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